Prf1

Summary

Gene Symbol: Prf1
Description: perforin 1 (pore forming protein)
Alias: Pfn, Pfp, Prf-1, cytolysin, lymphocyte pore-forming protein, perforin-1, pore forming protein
Species: mouse

Top Publications

  1. ncbi Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice
    D Kagi
    Department of Pathology, University of Zurich, Switzerland
    Nature 369:31-7. 1994
  2. ncbi TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver
    Kazuyoshi Takeda
    Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bukyou ku, Tokyo 113 8421, Japan
    Blood 105:2082-9. 2005
  3. pmc Differential tumor surveillance by natural killer (NK) and NKT cells
    M J Smyth
    Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
    J Exp Med 191:661-8. 2000
  4. ncbi Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice
    Erika Cretney
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, A Beckett Street, East Melbourne, 8006 Victoria, Australia
    J Immunol 168:1356-61. 2002
  5. ncbi Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis
    S E Street
    Cancer Immunology, Peter MacCallum Cancer Institute, Victoria, Australia
    Blood 97:192-7. 2001
  6. ncbi Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes
    H Kojima
    Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan
    Immunity 1:357-64. 1994
  7. ncbi Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways
    B Lowin
    Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
    Nature 370:650-2. 1994
  8. pmc Perforin-expressing cytotoxic cells contribute to chronic cardiomyopathy in Trypanosoma cruzi infection
    Jaline Coutinho Silverio
    Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
    Int J Exp Pathol 91:72-86. 2010
  9. pmc Absence of perforin expression confers axonal protection despite demyelination
    Charles L Howe
    Department of Neuroscience, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA
    Neurobiol Dis 25:354-9. 2007
  10. ncbi Perforin-dependent neurologic injury in a viral model of multiple sclerosis
    P D Murray
    Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Neurosci 18:7306-14. 1998

Research Grants

  1. The regulation of tumor immunity by NKT cells
    Mark Smyth; Fiscal Year: 2007
  2. Early T cell checkpoint violation in NOD mice
    Mary A Yui; Fiscal Year: 2010
  3. Early T cell checkpoint violation in NOD mice
    Mary A Yui; Fiscal Year: 2010
  4. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2007
  5. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2007
  6. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2007
  7. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2006
  8. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2010
  9. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2010
  10. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2010

Detail Information

Publications138 found, 100 shown here

  1. ncbi Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice
    D Kagi
    Department of Pathology, University of Zurich, Switzerland
    Nature 369:31-7. 1994
    ..The mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumour cells with reduced efficiency. Perforin is therefore a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis...
  2. ncbi TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver
    Kazuyoshi Takeda
    Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bukyou ku, Tokyo 113 8421, Japan
    Blood 105:2082-9. 2005
    ..This study is the first to describe the concomitant maturation of NK cell effector function with surface phenotype in vivo and implies an important defense role for NK cell TRAIL in the developing immune system...
  3. pmc Differential tumor surveillance by natural killer (NK) and NKT cells
    M J Smyth
    Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
    J Exp Med 191:661-8. 2000
    ..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide...
  4. ncbi Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice
    Erika Cretney
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, A Beckett Street, East Melbourne, 8006 Victoria, Australia
    J Immunol 168:1356-61. 2002
    ..TRAIL gene-targeted mice were also more sensitive to the chemical carcinogen methylcholanthrene. These results substantiated TRAIL as an important natural effector molecule used in the host defense against transformed cells...
  5. ncbi Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis
    S E Street
    Cancer Immunology, Peter MacCallum Cancer Institute, Victoria, Australia
    Blood 97:192-7. 2001
    Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity...
  6. ncbi Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes
    H Kojima
    Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan
    Immunity 1:357-64. 1994
    ..These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis...
  7. ncbi Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways
    B Lowin
    Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
    Nature 370:650-2. 1994
    ..Thus, two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand-receptor interaction...
  8. pmc Perforin-expressing cytotoxic cells contribute to chronic cardiomyopathy in Trypanosoma cruzi infection
    Jaline Coutinho Silverio
    Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
    Int J Exp Pathol 91:72-86. 2010
    ..cruzi strain. This protocol led to acute phase survival in both wild-type and perforin null (pfp(-/-)) mice lineages...
  9. pmc Absence of perforin expression confers axonal protection despite demyelination
    Charles L Howe
    Department of Neuroscience, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA
    Neurobiol Dis 25:354-9. 2007
    ..We conclude that perforin-dependent effector cells such as cytotoxic T cells, gammadelta T cells, and natural killer cells may play a role in axon damage that is dependent upon but separable from demyelination...
  10. ncbi Perforin-dependent neurologic injury in a viral model of multiple sclerosis
    P D Murray
    Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Neurosci 18:7306-14. 1998
    ..These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination...
  11. pmc The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice
    M B Baker
    Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA
    J Exp Med 183:2645-56. 1996
    ..In addition, perforin-mediated anti-recipient cytotoxicity appears to play an important role in the kinetics of GVHD pathophysiology, but is not required for GVHD-associated tissue damage...
  12. pmc Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells
    Shayna E A Street
    Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre Peter Mac, 8006, Victoria, Australia
    J Exp Med 199:879-84. 2004
    ..These results reflect a critical role for NK cells and gammadeltaTCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition...
  13. ncbi Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis
    Josianne Nitcheu
    Institut National de la Sante et de la Recherche Medicale, Unité 511, Immunobiologie Cellulaire et Moleculaire des Infections Parasitaires, CHU Pitie Salpetriere, Universite Pierre et Marie Curie, 91 Boulevard de l Hopital, 75634 Paris Cedex 13, France
    J Immunol 170:2221-8. 2003
    ..We found that, in contrast to ECM-susceptible C57BL6 mice, perforin-deficient (PFP-KO) mice were resistant to ECM in the absence of brain lesions, whereas cytoadherence of parasitized erythrocytes ..
  14. ncbi An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder
    Michael B Jordan
    Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, USA
    Blood 104:735-43. 2004
    ..These studies provide insight into the pathophysiology of HLH, and provide new targets for specific therapeutic intervention in this fatal disorder...
  15. ncbi Perforin/Fas-ligand double deficiency is associated with macrophage expansion and severe pancreatitis
    J Spielman
    Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33136, USA
    J Immunol 161:7063-70. 1998
    ..These studies demonstrate a novel role for perforin in homeostatic regulation of the immune response...
  16. pmc Ectopic T-cell specificity and absence of perforin and granzyme B alleviate neural damage in oligodendrocyte mutant mice
    Antje Kroner
    Department of Neurology, Section of Developmental Neurobiology, University of Wuerzburg, Josef Schneider Str 11, D 97080 Wuerzburg, Germany
    Am J Pathol 176:549-55. 2010
    ..These findings have high relevance with regard to our understanding of the pathogenesis of disorders primarily caused by genetically mediated oligodendropathy...
  17. pmc A null mutation in the perforin gene impairs cytolytic T lymphocyte- and natural killer cell-mediated cytotoxicity
    B Lowin
    Institute of Biochemistry, University of Lausanne, Switzerland
    Proc Natl Acad Sci U S A 91:11571-5. 1994
    ..We conclude that perforin is a crucial effector molecule in T cell- and NK cell-mediated cytolysis. However, alternative perforin-independent lytic mechanisms also exist...
  18. ncbi Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma
    V P Badovinac
    Department of Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
    Science 290:1354-8. 2000
    ..Thus, perforin and IFN-gamma regulate distinct elements of CD8+ T cell homeostasis independently of their role as antimicrobial effector molecules...
  19. pmc Immune function in mice lacking the perforin gene
    C M Walsh
    Department of Biology, University of California, Los Angeles 90024
    Proc Natl Acad Sci U S A 91:10854-8. 1994
    ..We conclude that perforin-less -/- mice retain and express the Fas lytic pathway as expressed in vitro but that this pathway is insufficient to clear an LCMV infection in vivo...
  20. ncbi Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin
    J Pardo
    Metschnikoff Laboratory, Max Planck Institut for Immunbiology, Stubeweg 51, Freiburg, Germany
    Cell Death Differ 14:1768-79. 2007
    ..The data suggest that activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues...
  21. ncbi IL-21 induces the functional maturation of murine NK cells
    Jason Brady
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    J Immunol 172:2048-58. 2004
    ..These developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance...
  22. pmc Decreased tumor surveillance in perforin-deficient mice
    M E van den Broek
    Institute of Experimental Immunology, University of Zurich, Switzerland
    J Exp Med 184:1781-90. 1996
    ....
  23. ncbi Cutting edge: granzymes A and B are not essential for perforin-mediated tumor rejection
    Mark J Smyth
    Cancer Immunology Program, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia
    J Immunol 171:515-8. 2003
    ....
  24. ncbi NK cell-mediated immunopathology during an acute viral infection of the CNS
    Mohammed Alsharifi
    Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, Australia
    Eur J Immunol 36:887-96. 2006
    ..This is the first study illustrating an NK cell-mediated immunopathological outcome to an acute viral infection...
  25. pmc Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease
    Linrong Lu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:19420-5. 2008
    ..Further analysis revealed that genetic disruption of the Qa-1-CD94/NKG2A interaction unleashes robust CD8 Treg cell activity that completely abolishes development of EAE...
  26. ncbi Murine cytomegalovirus replication in salivary glands is controlled by both perforin and granzymes during acute infection
    L Riera
    Department of Public Health and Microbiology, Medical School, Torino, Italy
    Eur J Immunol 30:1350-5. 2000
    ....
  27. ncbi Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs
    Todd A Fehniger
    Division of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 26:798-811. 2007
    ..These data suggest that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation...
  28. ncbi Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity
    D Kagi
    Department of Pathology, University of Zurich, Switzerland
    Science 265:528-30. 1994
    ..All cytotoxicity observed was due to either of these mechanisms, and no third mechanism was detected. Thus, the perforin- and Fas-based mechanisms may account for all T cell-mediated cytotoxicity in short-term in vitro assays...
  29. pmc Genomic organization of the mouse pore-forming protein (perforin) gene and localization to chromosome 10. Similarities to and differences from C9
    J A Trapani
    Laboratory of Human Immunogenetics, Memorial Sloan Kettering Cancer Center, New York, New York 10021
    J Exp Med 171:545-57. 1990
    Genomic clones encompassing the entire coding region of the mouse lymphocyte pore-forming protein gene (Pfp) have been isolated and used to determine its intron-exon organization...
  30. pmc Suppression of lymphoma and epithelial malignancies effected by interferon gamma
    Shayna E A Street
    Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia
    J Exp Med 196:129-34. 2002
    ..we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-gamma and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF)...
  31. pmc Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells
    C H Tay
    Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
    J Virol 71:267-75. 1997
    ..These results may explain why the Cmv-lr locus, which maps closely to genes regulating NK cell cytotoxic function, confers an NK cell-dependent resistance to MCMV infection in the spleen but not in the liver...
  32. pmc Natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver
    Joy Loh
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Virol 79:661-7. 2005
    ..of the acute phase of murine cytomegalovirus (MCMV) infection and have been reported to utilize perforin (Pfp)- and gamma interferon (IFN-gamma)-dependent effector mechanisms in an organ-specific manner to regulate MCMV ..
  33. ncbi IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma
    Hak Ling Ma
    Wyeth Research, Cambridge, MA 02140, USA
    J Immunol 171:608-15. 2003
    ..We conclude that IL-21 immunotherapy warrants clinical evaluation as a potential treatment for cancer...
  34. pmc West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection
    James D Brien
    Department of Molecular Microbiology and Immunology, Oregon National Primate Research Center, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
    J Immunol 181:8568-75. 2008
    ..These results demonstrate the role of direct effector function of Ag-specific CD4 T cells in preventing severe WNV disease...
  35. ncbi Perforin is a major contributor to NK cell control of tumor metastasis
    M J Smyth
    Cellular Immunity Laboratory, Austin Research Institute, Heidelberg, Victoria, Australia
    J Immunol 162:6658-62. 1999
    ..Depletion of NK subsets resulted in greater numbers of metastases than observed in perforin-deficient mice, suggesting that perforin-independent effector functions of NK cells may also contribute to protection from tumor metastasis...
  36. pmc Reduced incidence and delayed onset of diabetes in perforin-deficient nonobese diabetic mice
    D Kagi
    Ontario Cancer Institute, Toronto M5G2M9, Canada
    J Exp Med 186:989-97. 1997
    ..However, in the absence of perforin chronic inflammation of the islets can lead to diabetogenic beta cell loss by less efficient secondary effector mechanisms...
  37. pmc In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells
    M M Simon
    Max Planck Institut für Immunbiology, Freiburg, Germany
    J Exp Med 186:1781-6. 1997
    ..This suggests that gzmA and B are critical for Tc/NK granule- mediated nucleolysis, with gzmB being the main contributor, while target cell lysis is due solely to perforin and independent of both proteases...
  38. pmc Demyelinated axons and motor function are protected by genetic deletion of perforin in a mouse model of multiple sclerosis
    Chandra Deb
    Departments of Neurology, Mayo Clinic, Rochester, Minnesota
    J Neuropathol Exp Neurol 68:1037-48. 2009
    ..These results suggest that perforin is a key mediator of axon injury and lend additional support to the hypothesis that CD8 T cells are primarily responsible for axon damage in multiple sclerosis...
  39. ncbi Perforin protects against autoimmunity in lupus-prone mice
    S L Peng
    Department of Biology, Yale University, New Haven, CT 06510, USA
    J Immunol 160:652-60. 1998
    ....
  40. ncbi Myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas- and Fas ligand-deficient lpr and gld mice
    U Malipiero
    Department of Neurosurgery, University Hospital Zurich, Switzerland
    Eur J Immunol 27:3151-60. 1997
    ..Unlike oligodendrocytes, astrocytes were killed by FasL in vitro. It remains to be established whether this latter finding explains the different disease course of lpr and gld mice compared to wild-type and perforin knockout mice...
  41. ncbi Perforin and granzymes have distinct roles in defensive immunity and immunopathology
    Serani L H van Dommelen
    Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Western Australia, Australia
    Immunity 25:835-48. 2006
    ..Here we showed that perforin (Prf1) and granzymes (Gzms) have distinct roles in defensive immunity and immunopathology in a well-established model of ..
  42. pmc Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes
    A Mullbacher
    Division of Immunology, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
    Proc Natl Acad Sci U S A 96:13950-5. 1999
    ..These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens...
  43. ncbi Perforin-dependent cytolytic responses in beta2-microglobulin-deficient mice
    M J Smyth
    Cellular Cytotoxicity Laboratory, The Austin Research Institute, Studley Road, Heidelberg, Victoria, 3084, Australia
    Cell Immunol 196:51-9. 1999
    ..Dependence on perforin function was demonstrated for the cytotoxicity of these effectors in vitro and for the ability of these effectors to reject a variety of tumors in vivo...
  44. doi B-cells and IL-4 promote methylcholanthrene-induced carcinogenesis but there is no evidence for a role of T/NKT-cells and their effector molecules (Fas-ligand, TNF-α, perforin)
    Thomas Kammertoens
    Institut fur Immunologie, Charite, Campus Benjamin Franklin, Berlin, Germany
    Int J Cancer 131:1499-508. 2012
    ....
  45. pmc Densely granulated murine NK cells eradicate large solid tumors
    Rebecca B Liu
    Committee on Immunology, Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    Cancer Res 72:1964-74. 2012
    ..These results indicate that IL-15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors...
  46. pmc Mouse tumor vasculature expresses NKG2D ligands and can be targeted by chimeric NKG2D-modified T cells
    Tong Zhang
    Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA
    J Immunol 190:2455-63. 2013
    ..The in vivo antiangiogenesis effects mediated by chNKG2D-bearing T cells at the tumor site were dependent on IFN-γ and perforin. These results provide a novel mechanism for NKG2D-based targeting of solid tumors...
  47. pmc 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury
    Aaron M Fullerton
    Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, 1129 Farm Lane, Room 215, East Lansing, MI 48824, USA
    Toxicol Appl Pharmacol 266:317-27. 2013
    ..In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression...
  48. pmc Natural killer cells act as rheostats modulating antiviral T cells
    Stephen N Waggoner
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Nature 481:394-8. 2012
    ..Thus, NK cells can act as rheostats, regulating CD4 T-cell-mediated support for the antiviral CD8 T cells that control viral pathogenesis and persistence...
  49. pmc Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade
    Matthew Sharron
    Division of Critical Care Medicine, Children s National Medical Center, Washington, DC, United States of America
    PLoS ONE 7:e41549. 2012
    ..We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis...
  50. pmc Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice
    Helge Frebel
    Institute of Microbiology, ETH Zurich, 8093 Zurich, Switzerland
    J Exp Med 209:2485-99. 2012
    ....
  51. pmc Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity
    Robert Zeiser
    Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Blood 110:4588-98. 2007
    ....
  52. pmc Perforin deficiency attenuates collagen-induced arthritis
    Kristin Bauer
    Institute of Immunology, University of Rostock, Rostock, Germany
    Arthritis Res Ther 7:R877-84. 2005
    ..In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8+ T cells, for the pathogenesis of ..
  53. ncbi Prolonged production of TNF-alpha exacerbates illness during respiratory syncytial virus infection
    John A Rutigliano
    Vaccine Research Center National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 173:3408-17. 2004
    ..In addition, the revelation that TNF-alpha is the principal mediator of RSV-induced illness means that administration of TNF receptor antagonists, in combination with antiviral therapy, may be an effective method to treat RSV infections...
  54. pmc IFN-gamma-producing dendritic cells are important for priming of gut intraepithelial lymphocyte response against intracellular parasitic infection
    Magali M Moretto
    Department of Microbiology, Parasitology and Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    J Immunol 179:2485-92. 2007
    ..To our knowledge, this report is the first demonstrating a role for IFN-gamma-producing DC from Peyer's patches in the development of Ag-specific IEL population and their trafficking to the gut epithelium...
  55. pmc Up-regulation of Fas (CD95) expression in tumour cells in vivo
    Naama Peshes-Yaloz
    Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
    Immunology 120:502-11. 2007
    ..Our model is that host lymphoid cells in response to a tumour increase NO synthesis, which in turn causes enhanced Fas expression in the tumour...
  56. ncbi The role of TNF-TNFR2 interactions in generation of CTL responses and clearance of hepatic adenovirus infection
    Michel I Kafrouni
    Department of Internal Medicine, Divison of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, 75390 9151, USA
    J Leukoc Biol 74:564-71. 2003
    ..These findings indicate that TNF/TNFR2 interactions facilitate generation of FasL-dependent CTL effector pathways that play an important role in in vivo antiviral-immune responses in the liver...
  57. ncbi Cytotoxic T lymphocytes overcome Bcl-2 inhibition: target cells contribute to their own demise
    Ing Swie Goping
    Department of Biochemistry, University of Alberta, Edmonton, AB, Canada
    Blood 111:2142-51. 2008
    ..This ensures that CTLs can eliminate those target cells that have compromised apoptotic potential due to overexpression of Bcl-2...
  58. ncbi IL-21 enhances tumor rejection through a NKG2D-dependent mechanism
    Rayna Takaki
    Department of Microbiology and Immunology, Biomedical Sciences Graduate Program and The Cancer Research Institute, University of California, San Francisco, CA 94143, USA
    J Immunol 175:2167-73. 2005
    ..Collectively, these findings suggest that IL-21 therapy may work optimally against tumors that can elicit a NKG2D-mediated immune response...
  59. pmc 2B4 inhibits NK-cell fratricide
    Ruth T Taniguchi
    University of Chicago Department of Pathology, Committee on Immunology, Chicago, IL 60637, USA
    Blood 110:2020-3. 2007
    ..We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal...
  60. doi Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells
    Mathieu Epardaud
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Res 68:2972-83. 2008
    ....
  61. pmc IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis
    Michele W L Teng
    Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia
    Proc Natl Acad Sci U S A 107:8328-33. 2010
    ..Overall, these data indicate the general role that IL-23 plays in suppressing natural or cytokine-induced innate immunity, promoting tumor development and metastases independently of IL-17A...
  62. pmc In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia
    Jaebok Choi
    Division of Oncology, Department of Medicine, Washington University, St Louis, MO 63110, USA
    Blood 116:129-39. 2010
    ..Their suppressor function is dependent on direct contact, partially dependent on perforin 1 (Prf1), but independent of granzyme B (GzmB), and surprisingly, Foxp3...
  63. pmc Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency
    Gerhard Wingender
    Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
    J Immunol 185:2721-9. 2010
    ..Therefore, unlike NK cells, which rely mostly on perforin/granzyme-mediated mechanisms, the Ag-specific cytotoxicity of iNKT cells in vivo is largely restricted to the CD95/CD178 pathway...
  64. doi Administration of alpha-galactosylceramide impairs the survival of dendritic cell subpopulations in vivo
    Helen M A Simkins
    Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand
    J Leukoc Biol 89:753-62. 2011
    ..Thus, iNKT cells regulate the survival of CD8(+) DCs through a mechanism that does not appear to involve direct cell killing...
  65. ncbi Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a mechanism that is independent of CD95 and IFN-gamma but requires TNF-alpha
    D W White
    Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City 52242, USA
    J Immunol 160:898-905. 1998
    ..These results indicate that single Ag-specific CD8+ T cells derived from PO mice can mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN-gamma, but requires TNF-alpha...
  66. ncbi Regulation of perforin gene expression in a T cell hybrid with inducible cytolytic activity
    J A Garcia-Sanz
    Department of Microbiology and Immunology, University of Miami, School of Medicine
    Eur J Immunol 23:1877-83. 1993
    ..In addition, we confirm the existence of two types of mouse perforin mRNA that differ in their 5' untranslated regions, and show evidence that both mRNA are translated in vivo with similar efficiencies...
  67. ncbi Genetic mapping of gene encoding the farnesoid receptor, Fxr, to mouse Chromosome 10
    C A Kozak
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 0460, USA
    Mamm Genome 7:164-5. 1996
  68. ncbi Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locus
    Y Sunada
    Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242
    J Biol Chem 269:13729-32. 1994
    ....
  69. pmc CD8 T cell-initiated vascular endothelial growth factor expression promotes central nervous system vascular permeability under neuroinflammatory conditions
    Georgette L Suidan
    Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    J Immunol 184:1031-40. 2010
    ....
  70. ncbi Solid tumors "melt" from the inside after successful CD8 T cell attack
    Ulrike Blohm
    Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany
    Eur J Immunol 36:468-77. 2006
    ..Thus, our data also imply that adoptive transfer of tumor-specific CD8 T cells might synergize with radiation therapy or chemotherapy in the elimination of solid tumors in vivo...
  71. pmc Transmission of Toxoplasma gondii from infected dendritic cells to natural killer cells
    Catrine M Persson
    Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, F59, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Infect Immun 77:970-6. 2009
    ..These results suggest that rapid transfer of T. gondii from infected DC to effector NK cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection...
  72. ncbi Cutting edge: perforin down-regulates CD4 and CD8 T cell-mediated immune responses to a transplanted organ
    Anirban Bose
    Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
    J Immunol 170:1611-4. 2003
    ..In contrast, perforin did not influence T cell proliferation. Therefore, perforin is an essential immunoregulatory molecule that may be required for the induction of transplantation tolerance...
  73. pmc Interferon-gamma prevents death of bystander neurons during CD8 T cell responses in the brain
    Kirsten Richter
    Department of Virology, University of Freiburg, Freiburg, Germany
    Am J Pathol 174:1799-807. 2009
    ....
  74. doi Restricted Semliki Forest virus replication in perforin and Fas-ligand double-deficient mice
    Mohammed Alsharifi
    Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia
    J Gen Virol 89:1942-4. 2008
    ..Although the mechanism responsible for this observation is yet to be established, the lower virus titres found in these mice indicate that the role of cytolytic effector molecules in antiviral immunity needs to be re-evaluated...
  75. pmc CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumors
    Angela M Tatum
    Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Immunol 181:4406-17. 2008
    ..Finally, we show that production of IFN-gamma, but not perforin or TNF-alpha, by the donor lymphocytes is critical for control of autochthonous brain tumors...
  76. pmc NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responses
    Philippe Krebs
    Department of Genetics, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Blood 113:6593-602. 2009
    ..We think that the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development...
  77. pmc Protective immunity against secondary poxvirus infection is dependent on antibody but not on CD4 or CD8 T-cell function
    Vijay Panchanathan
    Infection and Immunology Group, Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Mills Road, Acton, ACT 0200, Australia
    J Virol 80:6333-8. 2006
    ..Thus, antibody is essential, but CD4 or CD8 T cells are not required for recovery from secondary poxvirus infection...
  78. ncbi Cytotoxic T lymphocytes from cathepsin B-deficient mice survive normally in vitro and in vivo after encountering and killing target cells
    Katherine Baran
    Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne 3002, Victoria, Australia
    J Biol Chem 281:30485-91. 2006
    ..We conclude that cathepsin B is not essential for protection of cytotoxic lymphocytes from the toxic effects of their secreted perforin...
  79. ncbi Cytotoxic T-cells from T-cell receptor transgenic NOD8.3 mice destroy beta-cells via the perforin and Fas pathways
    Nadine L Dudek
    St Vincent s Institute, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
    Diabetes 55:2412-8. 2006
    ..Therefore, NOD8.3 T-cells use both perforin and Fas pathways to kill beta-cells and the surprising blockade of NOD8.3 T-cell-mediated beta-cell death by SOCS-1 overexpression may be due in part to reduced target cell recognition...
  80. pmc Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and involves the BH3-only proteins Bid and Bim
    Thomas Kaufmann
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
    Immunity 30:56-66. 2009
    ..These observations identify caspase-8 and the BH3-only proteins Bid and Bim as potential therapeutic targets for treatment of inflammatory liver diseases...
  81. ncbi TCR transgenic CD8+ T cells activated in the presence of TGFbeta express FoxP3 and mediate linked suppression of primary immune responses and cardiac allograft rejection
    Judith A Kapp
    Department of Ophthalmology, Spain Wallace Building, 619 South 19th Street, University of Alabama at Birmingham, Birmingham, AL 35233 7331, USA
    Int Immunol 18:1549-62. 2006
    ..These data show that TGFbeta-activated CD8+ T cells mediate antigen-specific, APC-focused patterns of suppression in vitro and in vivo...
  82. pmc Regulation of perforin lysis: implications for protein disulfide isomerase proteins
    David L Tamang
    Department of Microbiology and Immunology MS320, University of Nevada, School of Medicine, Reno, NV 89557, USA
    Cell Immunol 255:82-92. 2009
    ..Our results indicate that protein disulfide isomerases, in the ER or elsewhere, may protect T cells from their own perforin...
  83. pmc Hydrolysis of tumor cell lipids after CTL-mediated death
    Bryce Alves
    Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Int Immunol 21:543-53. 2009
    ..Also, CTL-mediated death caused as much FA release as death by disruption of cells by freeze-thawing. The released oleic acid may be sufficient to promote secondary apoptotic responses after CTL-induced trauma...
  84. doi Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells
    Jennifer Fraszczak
    Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 866, Institut de Recherche Fédératif 100, Universite de Bourgogne, Dijon, France
    J Immunol 184:1876-84. 2010
    ....
  85. ncbi Dendritic cell apoptosis in the maintenance of immune tolerance
    Min Chen
    Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 311:1160-4. 2006
    ..The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance...
  86. pmc Critical role for perforin-, Fas/FasL-, and TNFR1-mediated cytotoxic pathways in down-regulation of antigen-specific T cells during persistent viral infection
    Shenghua Zhou
    Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA
    J Virol 76:829-40. 2002
    ..As expression of the Bcl-2 family members controls susceptibility to apoptosis, this finding may provide a molecular basis for the survival of anergic cells under conditions of prolonged antigen stimulation...
  87. ncbi Lesions of T-cell-mediated kidney allograft rejection in mice do not require perforin or granzymes A and B
    Philip F Halloran
    Department of Medicine, Division of Nephrology and Transplantation Immunology, University of Alberta, Edmonton, Alberta, Canada
    Am J Transplant 4:705-12. 2004
    ..Together with previous graft survival studies, these results indicate that the granule-associated cytotoxic mechanisms of T cells are not the effectors of T-cell-mediated allograft rejection...
  88. ncbi Cytokine deprivation of naive CD8+ T cells promotes minimal cell cycling but maximal cytokine synthesis and autonomous proliferation subsequently: a mechanism of self-regulation
    S Sad
    Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario
    J Immunol 163:2443-51. 1999
    ..These results suggest that the presence of excessive IL-2 during the activation of naive CD8+ T cells, while promoting cell cycling initially, may compromise long-term immunity...
  89. ncbi Natural killer cells do not mediate facial motoneuron survival after facial nerve transection
    Susanna C Byram
    Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA
    Brain Behav Immun 17:417-25. 2003
    ..Wild-type (WT), perforin/recombinase activating gene-2 knockout (pfp/RAG-2 KO), and common gamma-chain (gammac)/RAG-2 KO mice received a right facial nerve axotomy...
  90. ncbi Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers
    Kelly A Nordyke Messingham
    Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 171:4254-62. 2003
    ..Thus, increasing the number of memory CD8(+) T cells can overcome diminished per-cell protective immunity in the absence of perforin...
  91. ncbi Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism
    Bruce R Blazar
    University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN 55455, USA
    J Immunol 171:1272-7. 2003
    ..These data indicate that PD-1 ligation down-regulates GVHD through modulation of IFN-gamma production and suggest a novel therapeutic target for inhibiting GVHD lethality...
  92. ncbi Perforin-dependent activation-induced cell death acts through caspase 3 but not through caspases 8 or 9
    Liane Chen
    Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Eur J Immunol 33:769-78. 2003
    ..Thus, perforin-dependent early AICD appears to require activation of caspase 3, but not caspases 8 or 9. As perforin has no intrinsic catalytic abilities, we propose that it releases some endogenous activity that can activate caspase 3...
  93. ncbi T-cells mediate an inhibitory effect of interleukin-4 on osteoclastogenesis
    Danijela Mirosavljevic
    St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
    J Bone Miner Res 18:984-93. 2003
    ....
  94. ncbi Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice
    Vladimir P Badovinac
    Department of Microbiology, University of Iowa, Iowa City 52242, USA
    Immunity 18:463-74. 2003
    ..Thus, perforin was essential for resistance to secondary LCMV infection, and, in the absence of perforin, vaccination resulted in lethal disease mediated by dysregulated CD8(+) T cell expansion and cytokine production...
  95. ncbi Perforin-mediated effector function within the central nervous system requires IFN-gamma-mediated MHC up-regulation
    Cornelia C Bergmann
    Department of Neurology, Keck School of Medicine, University of California, Los Angeles, CA 90033, USA
    J Immunol 170:3204-13. 2003
    ..The data further imply that IFN-gamma plays a crucial role in pathogenesis by regulating the balance between virus replication in oligodendrocytes, CD8(+) T cell effector function, and demyelination...
  96. pmc Pathogenesis of herpes simplex virus type 1-induced corneal inflammation in perforin-deficient mice
    E Chang
    Department of Molecular Microbiology Immunology, School of Medicine, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211, USA
    J Virol 74:11832-40. 2000
    ..There was no significant difference between the infectious viral titers isolated from the eyes of PKO and wild-type mice. Our findings show that perforin is important in the pathogenesis of HSK...
  97. ncbi The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells
    H Daniel Lacorazza
    Laboratory of Molecular Aspects of Hematopoiesis, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Immunity 17:437-49. 2002
    ..Our results uncover a specific role of MEF in the development and function of NK cells and in innate immunity...
  98. ncbi Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liver
    S Khan
    Research Department and Institute for Pathology, Cantonal Hospital St Gallen, St Gallen, Switzerland
    J Immunol 167:6859-68. 2001
    ....
  99. ncbi Analysis of regulatory CD8 T cells in Qa-1-deficient mice
    Dan Hu
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 5:516-23. 2004
    ..These findings delineate a Qa-1-dependent T cell-T cell inhibitory interaction that prevents the pathogenic expansion of autoreactive CD4 T cell populations and consequent autoimmune disease...
  100. pmc m144, a murine cytomegalovirus (MCMV)-encoded major histocompatibility complex class I homologue, confers tumor resistance to natural killer cell-mediated rejection
    E Cretney
    Cellular Immunity Laboratory, The Austin Research Institute, Melbourne, Victoria, Australia
    J Exp Med 190:435-44. 1999
    ....
  101. pmc Perforin and Fas cytolytic pathways coordinately shape the selection and diversity of CD8+-T-cell escape variants of influenza virus
    Graeme E Price
    Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, CB 2803, Augusta, Georgia 30912 3175, USA
    J Virol 79:8545-59. 2005
    ..We conclude that selection of viral CTL escape variants reflects coordinate action between the tightly controlled perforin/granzyme pathway and the more promiscuous Fas/FasL pathway...

Research Grants66

  1. The regulation of tumor immunity by NKT cells
    Mark Smyth; Fiscal Year: 2007
    ..This proposal focuses clearly on a pivotal immune control mechanism that will influence many current and future immunotherapies. ..
  2. Early T cell checkpoint violation in NOD mice
    Mary A Yui; Fiscal Year: 2010
    ..Identifying genes and pathways affectingT cells, which predispose NOD mice to T1D will help in the understanding of immune deviations that can lead to disease in humans. ..
  3. Early T cell checkpoint violation in NOD mice
    Mary A Yui; Fiscal Year: 2010
    ..Identifying genes and pathways affectingT cells, which predispose NOD mice to T1D will help in the understanding of immune deviations that can lead to disease in humans. ..
  4. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2007
    ..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
  5. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2007
    ..These studies will lead to improved strategies for re-establishing immune privilege of corneal transplants and offsetting the untoward effects of allergic diseases on the fate of corneal transplants. ..
  6. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2007
    ....
  7. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2006
    ..All three of these aims will be addressed in a well-characterized mouse model of penetrating keratoplasty. ..
  8. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2010
    ..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
  9. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2010
    ..These studies will lead to improved strategies for re-establishing immune privilege of corneal transplants and offsetting the untoward effects of allergic diseases on the fate of corneal transplants. ..
  10. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2010
    ..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
  11. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2010
    ....
  12. An Animal Model of Hemophagocytic Lymphohistiocytosis
    Michael Jordan; Fiscal Year: 2009
    ..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
  13. IMMUNOLOGICAL MODULATION OF OCULAR TUMOR METASTASES
    Jerry Niederkorn; Fiscal Year: 2010
    ..The fourth aim will evaluate the therapeutic efficacy of a monoclonal antibody directed against human CD54 in controlling liver metastases in a nude mouse model of uveal melanoma. ..
  14. Mechanisms of neuronal injury during virus infection of the CNS
    Charles Howe; Fiscal Year: 2009
    ..Importantly, we have found that treatment with an FDA-approved drug protects neurons and cognitive function without altering the ability of the immune system to clear the virus from the brain. ..
  15. Immune response to Pneumocystis and bone marrow failure
    Nicole Meissner; Fiscal Year: 2009
    ..Understanding how the immune system supports hematopoiesis is needed to develop strategies for the prevention and treatment of pancytopenia in AIDS patients. ..
  16. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2009
    ....
  17. In Situ Analysis of Hepatitis B virus-specific T cells
    Dorian McGavern; Fiscal Year: 2006
    ..The main objective of this research is to more precisely define the contribution of HBV-specific CTL to viral clearance and pathogenesis by providing the first comprehensive analysis of these cells in situ. ..
  18. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2006
    ..g., corneal transplantation). In some cases, it may be desirable to abrogate immune privilege to promote the immune-rejection of sight- and life-threatening ocular neoplasms. ..
  19. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 1993
    ..The results from these investigations should provide important insights into the immunobiology of corneal allografts and the feasibility of specific immunological strategies for promoting corneal allograft survival...
  20. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 1993
    ..The long range goals of this project are to understand immune regulatory processes in the eye and to manipulate such processes to reduce immune-mediated injury and corneal graft rejection...
  21. B Cell Expansion After Dendritic Cell Immunization
    Michael Jordan; Fiscal Year: 2004
    ..My near term career path will involve ongoing basic research and study in order to improve my ultimate scientific productivity. ..
  22. T cell Interactions in the CNS During Viral Persistence
    Dorian McGavern; Fiscal Year: 2005
    ..The main objective of this research is to define the immunologic parameters that contribute to viral clearance versus persistence in the CNS and foster approaches that tip the balance in favor of clearance. ..
  23. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2003
    ..g., corneal transplantation). In some cases, it may be desirable to abrogate immune privilege to promote the immune-rejection of sight- and life-threatening ocular neoplasms. ..
  24. TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYE
    Jerry Niederkorn; Fiscal Year: 2002
    ..g., corneal transplantation) or abrogate immune privilege to protect against sight- and life-threatening neoplasms. ..
  25. IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2001
    ..Both strategies procure antigen-specific suppression of host immune responses and should prove useful in preventing corneal graft rejection. ..